Kher A, Bara L, Samama M
Pathol Biol (Paris). 1986 Jan;34(1):61-9.
Heparin is a heterogeneous component consisting of anionic polysaccharides chains of variable molecular weight ranging from 3 000 to 40 000 daltons. It is by potentiating antithrombin III (AT III) a natural inhibitor of coagulation, that heparin exerts its anticoagulant effect. Actually, it has been demonstrated that only 30% of the molecule in commercial heparin preparations are capable of binding to AT III: moreover, several procedures were used to prepare low molecular weight heparin fractions or fragments. These preparations were lacking in ability to prolong the clotting time (APTT) and to inhibit thrombin, but were capable of potentiating the inhibition of factor Xa. The hypothesis that low molecular weight heparins may exhibit antithrombotic effect by inhibition the coagulation cascade system at the initial stages is very attractive. Moreover, on animal models, heparin fractions with molecular weight less than 3 000 had limited ability to prevent experimental thrombosis despite good anti-Xa activity. Thus, the anti-Xa activity did not alone reflect the antithrombotic effect. Experimental studies have shown less bleeding with low molecular weight heparins compared to standard heparin. Some data have suggested other properties of low molecular weight heparins such as enhancement of fibrinolysis and a slighter effect on platelets. The risk of thrombocytopenia induced heparin could be reduced by the use of low molecular weight heparins. The pharmacokinetics of low molecular weight heparins have been studied in human subjects. A higher bioavailability and a longer duration of action were reported compared to heparin. Preliminary clinical trials have shown that one daily injection is sufficient to protect against post-operative thrombosis.
肝素是一种异质成分,由分子量在3000至40000道尔顿之间的可变阴离子多糖链组成。肝素通过增强抗凝血酶III(AT III)(一种天然的凝血抑制剂)发挥其抗凝作用。实际上,已经证明商业肝素制剂中只有30%的分子能够与AT III结合:此外,还采用了几种方法来制备低分子量肝素级分或片段。这些制剂缺乏延长凝血时间(活化部分凝血活酶时间)和抑制凝血酶的能力,但能够增强对因子Xa的抑制作用。低分子量肝素可能通过在初始阶段抑制凝血级联系统而表现出抗血栓形成作用的假说很有吸引力。此外,在动物模型中,分子量小于3000的肝素级分尽管具有良好的抗Xa活性,但预防实验性血栓形成的能力有限。因此,抗Xa活性并不能单独反映抗血栓形成作用。实验研究表明,与标准肝素相比,低分子量肝素引起的出血较少。一些数据表明低分子量肝素具有其他特性,如增强纤维蛋白溶解作用和对血小板的影响较小。使用低分子量肝素可降低肝素诱导的血小板减少症的风险。已经在人体受试者中研究了低分子量肝素的药代动力学。与肝素相比,报告显示其生物利用度更高,作用持续时间更长。初步临床试验表明,每日注射一次足以预防术后血栓形成。